• PMID: 25631347
• Gene Name: CDH2
• Condition: Altered meiotic progression, subfertility
• Association: Associated
• Sex: Male
• Infertility type: Male infertility
• Other associated phenotypes: Altered meiotic progression, subfertility

Specific deletion of Cdh2 in Sertoli cells leads to altered meiotic progression and subfertility of mice

Jiang X, Ma T, Zhang Y, Zhang H, Yin S, Zheng W, Wang L, Wang Z, Khan M, Sheikh SW, Bukhari I, Iqbal F, Cooke HJ, Shi Q.

CDH2 (cadherin 2, Neural-cadherin, or N-cadherin) is the predominant protein of testicular basal ectoplasmic specializations (basal ES; a testis-specific type of adhesion junction), one of the major cell junctions composing the blood-testis barrier (BTB). The BTB is found between adjacent Sertoli cells in seminiferous tubules, which divides the tubules into basal and adluminal compartments and prevents the deleterious exchange of macromolecules between blood and seminiferous tubules. However, the exact roles of basal ES protein CDH2 in BTB function and spermatogenesis is still unknown. We thus generated mice with Cdh2 specifically knocked out in Sertoli cells by crossing Cdh2 loxP mice with Amh-Cre mice. Cdh2 deletion in Sertoli cells did not affect Sertoli cell counts, but led to compromised BTB function, delayed meiotic progression from prophase to metaphase I in testes, increased germ cell apoptosis, sloughing of meiotic cells, and, subsequently, reduced sperm counts in epididymides and subfertility of mice. However, the testes with Cdh2-specific deletion in germ cells did not show any difference from the normal control testes, and phenotypes observed in Sertoli cell and germ cell Cdh2 double-knockout mice were indistinguishable from those in mice with Cdh2 specifically knocked out only in Sertoli cells. Taken together, our data demonstrate that the adhesion junction component, Cdh2, functions just in Sertoli cells, but not in germ cells during spermatogenesis, and is essential for the integrity of BTB function, its deletion in Sertoli cells would lead to the BTB damage and subsequently meiosis and spermatogenesis failure. CI - © 2015 by the Society for the Study of Reproduction, Inc. FAU - Jiang, Xiaohua AU - Jiang X AD - Laboratory of Molecular and Cell Genetics, Chinese Academy of Sciences (CAS) Key Laboratory of Innate Immunity and Chronic Disease, CAS Hefei Institutes of Physical Science, Hefei National Laboratory for Physical Sciences at Microscale, School of Life Sciences, University of Science & Technology of China, Hefei, China. FAU - Ma, Tieliang AU - Ma T AD - Laboratory of Molecular and Cell Genetics, Chinese Academy of Sciences (CAS) Key Laboratory of Innate Immunity and Chronic Disease, CAS Hefei Institutes of Physical Science, Hefei National Laboratory for Physical Sciences at Microscale, School of Life Sciences, University of Science & Technology of China, Hefei, China. FAU - Zhang, Yuanwei AU - Zhang Y AD - Laboratory of Molecular and Cell Genetics, Chinese Academy of Sciences (CAS) Key Laboratory of Innate Immunity and Chronic Disease, CAS Hefei Institutes of Physical Science, Hefei National Laboratory for Physical Sciences at Microscale, School of Life Sciences, University of Science & Technology of China, Hefei, China. FAU - Zhang, Huan AU - Zhang H AD - Laboratory of Molecular and Cell Genetics, Chinese Academy of Sciences (CAS) Key Laboratory of Innate Immunity and Chronic Disease, CAS Hefei Institutes of Physical Science, Hefei National Laboratory for Physical Sciences at Microscale, School of Life Sciences, University of Science & Technology of China, Hefei, China. FAU - Yin, Shi AU - Yin S AD - Laboratory of Molecular and Cell Genetics, Chinese Academy of Sciences (CAS) Key Laboratory of Innate Immunity and Chronic Disease, CAS Hefei Institutes of Physical Science, Hefei National Laboratory for Physical Sciences at Microscale, School of Life Sciences, University of Science & Technology of China, Hefei, China. FAU - Zheng, Wei AU - Zheng W AD - Laboratory of Molecular and Cell Genetics, Chinese Academy of Sciences (CAS) Key Laboratory of Innate Immunity and Chronic Disease, CAS Hefei Institutes of Physical Science, Hefei National Laboratory for Physical Sciences at Microscale, School of Life Sciences, University of Science & Technology of China, Hefei, China. FAU - Wang, Liu AU - Wang L AD - Laboratory of Molecular and Cell Genetics, Chinese Academy of Sciences (CAS) Key Laboratory of Innate Immunity and Chronic Disease, CAS Hefei Institutes of Physical Science, Hefei National Laboratory for Physical Sciences at Microscale, School of Life Sciences, University of Science & Technology of China, Hefei, China. FAU - Wang, Zheng AU - Wang Z AD - Laboratory of Molecular and Cell Genetics, Chinese Academy of Sciences (CAS) Key Laboratory of Innate Immunity and Chronic Disease, CAS Hefei Institutes of Physical Science, Hefei National Laboratory for Physical Sciences at Microscale, School of Life Sciences, University of Science & Technology of China, Hefei, China. FAU - Khan, Manan AU - Khan M AD - Laboratory of Molecular and Cell Genetics, Chinese Academy of Sciences (CAS) Key Laboratory of Innate Immunity and Chronic Disease, CAS Hefei Institutes of Physical Science, Hefei National Laboratory for Physical Sciences at Microscale, School of Life Sciences, University of Science & Technology of China, Hefei, China. FAU - Sheikh, Salma W AU - Sheikh SW AD - Laboratory of Molecular and Cell Genetics, Chinese Academy of Sciences (CAS) Key Laboratory of Innate Immunity and Chronic Disease, CAS Hefei Institutes of Physical Science, Hefei National Laboratory for Physical Sciences at Microscale, School of Life Sciences, University of Science & Technology of China, Hefei, China. FAU - Bukhari, Ihtisham AU - Bukhari I AD - Laboratory of Molecular and Cell Genetics, Chinese Academy of Sciences (CAS) Key Laboratory of Innate Immunity and Chronic Disease, CAS Hefei Institutes of Physical Science, Hefei National Laboratory for Physical Sciences at Microscale, School of Life Sciences, University of Science & Technology of China, Hefei, China. FAU - Iqbal, Furhan AU - Iqbal F AD - Laboratory of Molecular and Cell Genetics, Chinese Academy of Sciences (CAS) Key Laboratory of Innate Immunity and Chronic Disease, CAS Hefei Institutes of Physical Science, Hefei National Laboratory for Physical Sciences at Microscale, School of Life Sciences, University of Science & Technology of China, Hefei, China Institute of Pure and Applied Biology, Zoology Division. Bahauddin Zakariya University, Multan, Pakistan. FAU - Cooke, Howard J AU - Cooke HJ AD - Laboratory of Molecular and Cell Genetics, Chinese Academy of Sciences (CAS) Key Laboratory of Innate Immunity and Chronic Disease, CAS Hefei Institutes of Physical Science, Hefei National Laboratory for Physical Sciences at Microscale, School of Life Sciences, University of Science & Technology of China, Hefei, China Medical Research Council Human Genetics Unit and Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom.